Comparison of gene expression profiles between paired primary and metastasis colorectal carcinoma
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ABSTRACT: Paired tissues (normal colon, primary colorectal carcinoma, normal liver, liver metastasis of colorectal carcinoma) from 2 colorectal carcinoma patients in Taiwan were processed to generate total RNA, which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays. Comparison of gene expression profiles between paired normal colon and primary colorectal carcinoma; between primary colorectal carcinoma and liver metastasis colorectal carcinoma
Project description:Paired tissues (normal colon, primary colorectal carcinoma, normal liver, liver metastasis of colorectal carcinoma) from 2 colorectal carcinoma patients in Taiwan were processed to generate total RNA, which was subsequently analyzed for gene expression using Affymetrix U133 plus 2.0 arrays.
Project description:Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. Keywords: gene expression profiling using cDNA microarray We performed 17K cDNA microarray with the amplified RNAs from the following tissue samples: normal colorectal mucosa, primary colorectal tumors, normal liver and liver metastasis tumors, and primary colorectal tumors without liver metastasis. Organ-specific genes in normal colon and liver tissues were excluded from the pre-filtered genes, and then we discovered and validated liver metastasis-specific genes commonly up-regulated in the primary colorectal tumors and liver metastasis tumors. To confirm the microarray data, we performed a RT-PCR of two genes (WNT5A and carbonic anhydrase II) in the primary colorectal tumors with and without liver metastases.
Project description:Liver metastasis is one of the major causes of death in colorectal cancer (CRC) patients. To understand this process, we investigated whether the gene expression profiling of matched colorectal carcinomas and liver metastases could reveal key molecular events involved in tumor progression and metastasis. We performed experiments using a cDNA microarray containing 17,104 genes with the following tissue samples: paired tissues of 25 normal colorectal mucosa, 27 primary colorectal tumors, 13 normal liver and 27 liver metastasis, and 20 primary colorectal tumors without liver metastasis. To remove the effect of normal cell contamination, we selected 4,583 organ-specific genes with a false discovery rate (FDR) of 0.0067% by comparing normal colon and liver tissues using significant analysis of microarray, and these genes were excluded from further analysis. We then identified and validated 46 liver metastasis-specific genes with an accuracy of 83.3% by comparing the expression of paired primary colorectal tumors and liver metastases using prediction analysis of microarray. The 46 selected genes contained several known oncogenes and 2 ESTs. To confirm that the results correlated with the microarray expression patterns, we performed RT-PCR with WNT5A and carbonic anhydrase II. Additionally, we observed that 21 of the 46 genes were differentially expressed (FDR = 2.27%) in primary tumors with synchronous liver metastasis compared with primary tumors without liver metastasis. We scanned the human genome using a cDNA microarray and identified 46 genes that may play an important role in the progression of liver metastasis in CRC. Keywords: gene expression profiling using cDNA microarray
Project description:Genome wide miRNA expression profiling was performed using Affymetric miRNA v. 3.0 Array on 48 samples which included paired FFPE colon tuomor and metastisized liver and paired normal colon, normal liver). The data set was divided into two categories and identified by tissue source and patient demographics: Tissue (Colon, Liver), Source (Colon Tumor Liver Met, Colon Normal, Liver Normal), Sex (Male, Female), Patient Pair. microRNAs (miRs) are frequently dysregulated in colorectal cancer (CRC) and subsets are correlated with advanced tumor stage and metastasis. Despite this, the development of prognostic biomarkers that predict metastatic potential remain limited. Our study was designed to identify, validate, and elucidate underlying biology imposed by a miR signature that defines and predicts metastatic disease. Genome-wide miR expression profiling was performed on fourteen patient-matched stage IV primary CRC tumors and corresponding liver metastases using microRNA array technology. Based on these results, this miR panel was then validated and evaluated in normal colon tissue (N = 5), early stage (I & II, N = 11) and late stage (Stage III & IV, N = 14) colorectal primary tumors via qRT-PCR.
Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue RNA of 18 primary colorectal cancers, 18 matched liver metastases, 7 normal colon epithelium samples and 5 normal liver tissue samples hybridized on Human Sentrix-6 V2 (Illumina)
Project description:Comparison of expression profiles of primary colorectal cancers with liver metastases of the same patient. Additionally, expression data of normal colon and liver tissue. Abstract of publication will be included upon publication Keywords: expression profiling, colorectal cancer, colon cancer, liver metastasis, normal colonic tissue, normal liver tissue
Project description:Colorectal cancer (CRC) is one of the most prevalent cancers, with over one million new cases per year. Overall, prognosis of CRC largely depends on the disease stage and metastatic status. As precision oncology for patients with CRC continues to improve, this study aimed to integrate genomic, transcriptomic, and proteomic analyses to identify significant differences in expression during CRC progression using a unique set of paired patient samples while considering tumour heterogeneity.We analysed fresh-frozen tissue samples prepared under strict cryogenic conditions of matched healthy colon mucosa, colorectal carcinoma, and liver metastasis from the same patients. Somatic mutations of known cancer-related genes were analysed using Illumina's TruSeq Amplicon Cancer Panel; the transcriptome was assessed comprehensively using Clariom D microarrays. The global proteome was evaluated by liquid chromatography-coupled mass spectrometry (LC‒MS/MS) and validated by two-dimensional difference in-gel electrophoresis. Subsequent unsupervised principal component clustering, statistical comparisons, and gene set enrichment analyses were calculated based on differential expression results.Although panomics revealed low RNA and protein expression of CA1, CLCA1, MATN2, AHCYL2, and FCGBP in malignant tissues compared to healthy colon mucosa, no differentially expressed RNA or protein targets were detected between tumour and metastatic tissues. Subsequent intra-patient comparisons revealed highly specific expression differences (e.g., SRSF3, OLFM4, and CEACAM5) associated with patient-specific transcriptomes and proteomes.Our research results highlight the importance of inter- and intra-tumour heterogeneity as well as individual, patient-paired evaluations for clinical studies. In addition to changes among groups reflecting CRC progression, we identified significant expression differences between normal colon mucosa, primary tumour, and liver metastasis samples from individuals, which might accelerate implementation of precision oncology in the future.
Project description:Chromatin regulatory networks that maintain differentiated cell states are frequently dysregulated in and thus contribute to cancer metastasis. Here, we reveal the dynamic transitions of regulatory states of colorectal cancer (CRC) cells during metastasizing to liver by profiling single-cell chromatin accessibility of paired primary and metastatic CRC tumors in mouse. We discover CRC subclones, which are characterized by losing chromatin accessibility around colon-tissue specific genes and gain that around liver-specific genes,including transcription factors in FOXA family and HNF family we discovered in our previous study, might partially mimic types of liver cells across the liver development. A particular subclone with stem-like state, which is highly enriched in metastases but not primary tumors , clearly shows poor prognosis.
Project description:Somatic copy number alterations of 17 paired tumor and metastasis tissue samples were measured by Agilent array-based comparative genomic hybridization (CGH). Seven colon adenocarcinomas with paired liver metastasis and 10 liver carcinoma with metastasis to the lymph node, adrenal gland or lung were analyzed.
Project description:Comparison of genomic alterations of primary colorectal cancers with liver metastases of the same patient Keywords: array CGH, colorectal cancer, colon cancer, liver metastasis 21 primary colorectal cancers and 21 matched liver metastases hybridized against sex-matched control pools